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Medical Conditions

Acute Lymphoblastic Leukemia

Linda C. Stork, M.D.
Associate Professor, Pediatrics
University of Colorado School of Medicine
Pediatric Oncologist, The Children's Hospital

What is leukemia?

Leukemia is a cancer of the blood cells that begins in the bone marrow or the lymph glands where the blood cells are made. Bone marrow occupies the center of all bones, especially bones of the pelvis, the lower spine, and the thighs. Lymph nodes are all over the body, but they usually are too small to feel.

Like all cancers, leukemia is caused by uncontrolled cell division and growth. There are "signals" and "switches" within the genetic material and proteins of each cell of the body that strictly control whether the cells start or stop dividing to make more cells. For example, when a finger is cut, these "signals" and "switches" tell the skin cells to regrow just enough to replace the area of damaged skin and then to stop, without forming big lumps of skin.

Leukemia usually develops in the white blood cells that normally circulate through the blood stream and the lymph nodes to defend the body against infection. Leukemia begins in one cell whose "signals" and "switches" have stopped working correctly. This one abnormal cell divides into two abnormal cells, which divide into more and more abnormal cells. These leukemia cells eventually fill up the bone marrow space, thereby crowding out normal bone marrow cells and spreading into the blood stream and the lymph nodes. As a result, the cells that carry oxygen (red blood cells), the cells that help clot blood (platelets), and the normal white cells that fight infection are reduced greatly in number.

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What is acute lymphoblastic leukemia?

Acute lymphoblastic leukemia is the most common leukemia and cancer of childhood. The word "acute" refers to the fact that patients diagnosed with this leukemia in the early 20th century survived for only a short time. The word "lymphoblastic" refers to the type of white cell that has become cancer. Normal lymphoblasts mature over days to weeks into lymphocytes that defend against infection. Lymphoblasts of leukemia cannot mature or fight infection.

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What causes acute lymphoblastic leukemia?

The cause of this type of leukemia is unknown; therefore, it cannot be prevented at the present time. Several changes that occur in a normal lymphocyte over a period of time probably turn it into a leukemic cell. For some cases of acute lymphoblastic leukemia, the first change occurs in fetal life before birth.

Exposure to electrical power lines, toxic chemicals, radon, or radiation has not been proven to cause this leukemia. Although a specific virus causes leukemia in cats, viruses do not appear to cause acute lymphoblastic leukemia in children. This type of leukemia does not appear to be inherited because it very rarely occurs in more than one child per family.

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Who gets acute lymphoblastic leukemia?

Acute lymphoblastic leukemia is rare. Its incidence is fairly similar worldwide. In the United States, about 3,000 children are diagnosed with this disease each year. For children between infancy and 15 years, acute lymphoblastic leukemia occurs yearly in 1 child among every 25,000 children. For patients aged 2 to 6 years, acute lymphoblastic leukemia occurs yearly in 1 child among every 5,000 to 10,000 children. Although very rare, even newborns and adults can develop acute lymphoblastic leukemia. In the United States, acute lymphoblastic leukemia is much less common among African Americans than Caucasians; however, the reason for this difference is unclear.

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What are the common symptoms at diagnosis?

The symptoms of acute lymphoblastic leukemia often mimic more common illnesses of childhood. These symptoms are related to reduced numbers of normal bone marrow and blood cells. Patients develop anemia because of low numbers of the red blood cells; they often appear pale with fast heart rates, and, sometimes, they feel lightheaded and tire out easily. Patients with acute lymphoblastic leukemia often bruise more easily and get more nosebleeds because the cells that clot blood (platelets) are low in number. Patients often have several weeks of unexplained fever before acute lymphoblastic leukemia is diagnosed. Sometimes, these fevers are because of infections; other times, they are because of the leukemia itself. About 25% of patients experience bone pain for days to weeks before the diagnosis, especially in the pelvis, the spine, and the legs. About 50% of patients develop swollen lymph nodes in the neck, under the armpits, or in the groin. The liver and the spleen, usually tucked beneath the right and left lower rib cage in the abdomen, can enlarge and become painful as leukemic cells fill the many blood vessels within these organs. Occasionally, a boy's testicles swell as leukemic cells invade them. The lymph nodes deep within the chest may become swollen with leukemic cells, causing a child to breathe faster and harder than normal.

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How is acute lymphoblastic leukemia diagnosed?

The symptoms described above will prompt a physician to draw the child's blood for a complete blood count (CBC). Often, this CBC shows that the number of red blood cells, and/or platelets, and/or type of white cell called "neutrophils" is low. The total number of white cells in the CBC may range from very low to very high. The lymphoblasts may be recognized on the blood smear when viewed in the laboratory under the microscope.

The final diagnosis of acute lymphoblastic leukemia is made by a bone marrow examination. The bone marrow procedure entails placing a needle into the pelvic bone a few inches to the right or left of the spine and a few inches above the buttocks. This needle goes through the skin, the muscle, and the bone, and into the bone marrow space. From here, liquid bone marrow, filled with leukemic cells, is aspirated into an attached syringe. The bone marrow aspiration procedure is painful; a child usually is sedated and given pain medicine during the procedure.

Children with symptoms similar to those of patients with leukemia may have a different diagnosis. In those cases, the CBC is either completely normal or has abnormalities of only one blood cell type. Certain viral infections, joint diseases, or other blood diseases can mimic the symptoms of leukemia. Occasionally, children with acute lymphoblastic leukemia have symptoms of fever and bone or joint pain and a completely normal CBC. In such cases, the diagnosis is uncertain until the bone marrow aspiration shows the leukemia.

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How is acute lymphoblastic leukemia treated?

If untreated, acute lymphoblastic leukemia is a fatal disease. However, with modern day treatment, the majority of children with acute lymphoblastic leukemia are cured. Since the 1960s, many children with acute lymphoblastic leukemia and other cancers have participated in randomized clinical trials sponsored by national cooperative organizations, such as the Children's Cancer Group and the Pediatric Oncology Group. Major progress in the treatment of childhood cancers has been made because of the research efforts of these groups.

Children with leukemia are treated by pediatric oncologists and nurses in specialized facilities; patients and families usually are supported by social workers and child life specialists.

The medicines used to treat leukemia and other cancers are called chemotherapy. Chemotherapy drugs can be taken by mouth or injected into the blood stream through a vein, into soft tissue, or into muscle. Because leukemic cells tend to "hide out" in the lining of the brain and the spine, specific chemotherapy is injected into the spinal fluid by a procedure called a lumbar puncture. This procedure involves inserting a small needle into a space between two vertebrae of the lower spine, removing some spinal fluid, and injecting chemotherapy into the spinal fluid space. This procedure usually is performed with topical anesthetic and sedation.

Some of the chemotherapy drugs originally came from products of nature, such as the periwinkle and may apple plant or the bark of the yew tree, or from microorganisms, such as fungus. Other chemotherapy drugs were designed in laboratories. The first chemotherapy drug was developed in the late 1940s. Before that time, patients with acute lymphoblastic leukemia did not survive; all of them died of infection or bleeding within several months of diagnosis.

Treatment of acute lymphoblastic leukemia has evolved during the past 40 years; today, a child may receive up to 15 different chemotherapy drugs during a 2- to 3-year period. Occasionally, radiation therapy is given to the brain. After the first month of treatment, the child is usually in "remission"; 99% of the leukemia cells have been killed, and the CBC and the bone marrow look normal. During the next 2 to 3 years of treatment, chemotherapy attempts to kill the remaining 1% of leukemic cells, which are heartier than those initially killed.

For at least 70% of children, the leukemia never reappears, and these children grow up normally. If the leukemia recurs, it is called a "relapse" and is found in the blood and the bone marrow, the spinal fluid, or the testicles. A relapse can occur any time after remission, but it usually is between 18 months and 5 years after the initial diagnosis. A CBC is performed frequently, along with a physical exam, throughout the course of treatment and for many years thereafter to document continued remission or to diagnose a relapse. About 50% of patients who relapse can be cured with either bone marrow transplantation or several more years of intensive therapy.

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What are the complications?

Most patients require treatment with antibiotics and transfusions of red blood cells and platelets at diagnosis and during treatment. Once a child is in remission, complications of treatment are from side effects of chemotherapy and not from the leukemia itself. Chemotherapy drugs circulate throughout the entire blood stream and affect normal cells, especially those cells that are dividing rapidly. One common side effect is hair loss, which usually grows back after the first year of treatment. Some side effects can be prevented; most of them are reversible. Occasionally, a child in remission dies from a complication of treatment, usually an overwhelming infection.

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What research is being done?

Randomized clinical trials that aim to improve the cure rate of leukemia are being conducted by the Children's Oncology Group in most children's hospitals in the United States and Canada. Research on leukemic cells is being carried out in many laboratories throughout the world. The purpose of this research is to develop new strategies to treat leukemia; to determine what changes occur in a cell to cause leukemia; and, ultimately, to prevent a child from developing leukemia.

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Links to other information

For more information on acute lymphoblastic leukemia, log on to the following Web sites:

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References

Lilleyman JS. Childhood Leukemia: The Facts. Oxford, England: Oxford University Press; 1994.

Laszlo J. The Cure of Childhood Leukemia: Into the Age of Miracles. New Brunswick, NJ: Rutgers University Press; 1995.

Albano EA, Stork LC, Greffe BS, Odom LF, Foreman NK. Neoplastic disease. In: Hay W, Hayward A, eds. Current Pediatric Diagnosis and Treatment. Stanford, CT: Appleton & Lange; 1999:774-777.

About the Author

Dr. Stork is an associate professor of pediatrics at the University of Colorado Health Sciences Center and The Children's Hospital in Denver. She earned her undergraduate degree from Yale University and her medical degree from Columbia University. Dr. Stork is actively involved in clinical trials that treat children with acute lymphoblastic leukemia.

Copyright 2012 Linda C. Stork, M.D., All Rights Reserved

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